The major objective of this study is the development of safe and effective agents for the chemotherapy of all three major species of schistosomes infecting man. (1) Our earlier laboratory studies suggest that amoscanate (4-isothiocyanato-4'-nitrodiphenylamine) may be a highly promising chemotherapeutic agent for the treatment of schistosomiasis. Amoscanate has very low toxicity. It fails to produce resistant parasites. Cures of experimental infections with Schistosoma mansoni, S. japonicum and S. haematobium result from the administration of single, low, oral doses. Amoscanate is inexpensive, and formulated preparations are stable under field conditions. We propose to assemble all information on toxicology and efficacy and to submit this information together with a detailed protocol for a Phase I human trial to the U.S. Food and Drug Administration as an IND. Advance planning of field trials is under consideration. An integral aspect of these plans is further experimental work on the pharmacology, metabolism, and mode of action of amoscanate. (2) Studies are proposed on the mechanism of action and therapeutic efficacy of two other groups of antischistosomal agents: oltipraz and other diazinodithiolenes, and cyclosporin A. (3) An essential component of these studies and of other research programs in schistosomiasis at this institution and elsewhere is the maintenance of a facility capable of providing large quantities of: animals with standardized infections, cercariae, and other stages of the life cycle of various geographic strains of Schistosoma mansoni.